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Sample summary
Input data: infant stools (BS1, BS2, BS3, and BS5) and maternal stool (MS1)
- n samples = 2138
- n taxa: genera = 490; variants = 6282
- n taxa (rarefied): genera = 455; variants = 6143
Statistical methods for mixed-effects models
- Linear mixed-effects models fit with family ID as a random effect
- Association with ORV outcome determined by comparing fit of model with country/age vs model with age alone
Alpha diversity
Column
Genus-level
Seroconversion
Longitudinal plots
Statistics
Shannon log(Observed)
India 0.0099 0.0013
India (exposed) 0.3155 0.2959
India (unexposed) 0.0036 0.0001
Malawi 0.5418 0.5263
UK 0.8155 0.5826Post-ORV IgA
Dose 1 alpha diversity (week 6/8)
Correlation coefficients values
India India_exposed India_unexposed Malawi UK
Shannon -0.0194 0.0807 -0.1688 -0.3269 -0.0364
log(richness) -0.0538 0.0569 -0.1795 -0.2933 -0.0929P values
India India_exposed India_unexposed Malawi UK
Shannon 0.7429 0.3201 0.0530 0.0074 0.8061
log(richness) 0.3640 0.4834 0.0394 0.0169 0.5300Dose 2 alpha diversity (week 10/12)
Correlation coefficients values
India India_exposed India_unexposed Malawi UK
Shannon -0.0476 -0.0429 -0.0432 0.0767 -0.0630
log(richness) -0.0483 0.0600 -0.0950 -0.0380 0.0067P values
India India_exposed India_unexposed Malawi UK
Shannon 0.4272 0.5903 0.6393 0.5852 0.6670
log(richness) 0.4198 0.4507 0.3022 0.7870 0.9635Dose 1 shedding
Longitudinal plots
Statistics
Shannon log(Observed)
India 0.1704 0.1318
India (exposed) 0.8656 0.6844
India (unexposed) 0.2384 0.0572
Malawi 0.2673 0.1553Shedding after either dose
Longitudinal plots
Statistics
Shannon log(Observed)
India 0.3228 0.1297
India (exposed) 0.9722 0.6468
India (unexposed) 0.3455 0.1966
Malawi 0.9498 0.4796Neonatal infection
Longitudinal plots
Statistics
Shannon log(Observed)
India 0.4005 0.5271Cross-sectional comparisons
See Module 5 for full univariate and multivariate analyses.
RSV-level
Seroconversion
Longitudinal plots
Statistics
Shannon_rsv log(Observed_rsv)
India 0.0182 0.0044
India (exposed) 0.2923 0.3252
India (unexposed) 0.0156 0.0012
Malawi 0.9276 0.8659
UK 0.9307 0.5172Post-ORV IgA
Dose 1 alpha diversity (week 6/8)
Correlation coefficients values
India India_exposed India_unexposed Malawi UK
Shannon 0.0032 0.0729 -0.1138 -0.1374 -0.1349
log(richness) -0.0555 0.0416 -0.2035 -0.1915 -0.0843P values
India India_exposed India_unexposed Malawi UK
Shannon 0.9568 0.3690 0.1940 0.2711 0.3608
log(richness) 0.3487 0.6083 0.0192 0.1235 0.5689Dose 2 alpha diversity (week 10/12)
Correlation coefficients values
India India_exposed India_unexposed Malawi UK
Shannon -0.0254 -0.0476 0.0746 0.0942 -0.0103
log(richness) -0.0398 0.0065 -0.0616 -0.0251 -0.0544P values
India India_exposed India_unexposed Malawi UK
Shannon 0.6712 0.5502 0.4181 0.5023 0.9438
log(richness) 0.5062 0.9349 0.5036 0.8583 0.7107Dose 1 shedding
Longitudinal plots
Statistics
Shannon_rsv log(Observed_rsv)
India 0.5308 0.3872
India (exposed) 0.8026 0.6590
India (unexposed) 0.6945 0.2629
Malawi 0.1322 0.1664Shedding after either dose
Longitudinal plots
Statistics
Shannon_rsv log(Observed_rsv)
India 0.9686 0.3633
India (exposed) 0.8933 0.6198
India (unexposed) 0.9022 0.6262
Malawi 0.7173 0.9673Neonatal infection
Longitudinal plots
Statistics
Shannon_rsv log(Observed_rsv)
India 0.8768 0.64Beta diversity
Column
Genus-level
Seroconversion
Bray-Curtis distances (weighted)
Bray-Curtis distances (unweighted)
RSV-level
Seroconversion
Bray-Curtis distances (weighted)
Bray-Curtis distances (unweighted)
Differential taxa
Column
Genus-level
Seroconversion
Post-ORV IgA concentration
Dose 1 shedding
Shedding after either dose
Neonatal exposure
RSV-level
Seroconversion
Post-ORV IgA concentration
Dose 1 shedding
Shedding after either dose
Neonatal exposure
Longitudinal abundance comparisons
Immunogenicity
Number of infants/taxa included in longitudinal models:
- India (full), n infants: 305; n samples: 1140; n taxa: 25
- India (exposed), n infants: 166; n samples: 625; n taxa: 26
- India (unexposed), n infants: 138; n samples: 511; n taxa: 24
- Malawi, n infants: 96; n samples: 263; n taxa: 41
- UK, n infants: 51; n samples: 197; n taxa: 25
India
negatively correlated ns positively correlated
age 6 12 7
IgA 0 25 0
seroconv 0 25 0Summary statistics
[1] "No significant differences according to ORV outcome"India (exposed)
negatively correlated ns positively correlated
age 7 11 8
IgA 1 25 0
seroconv 0 26 0Summary statistics
taxon Estimate Std.Error padj comparison mean prev
59 Lactobacillus -0.181 0.055 0.0364 IgA 3.685 62.7India (unexposed)
negatively correlated ns positively correlated
age 6 10 8
IgA 0 24 0
seroconv 0 24 0Summary statistics
[1] "No significant differences according to ORV outcome"Malawi
negatively correlated ns positively correlated
age 12 14 15
IgA 0 41 0
seroconv 0 41 0Summary statistics
[1] "No significant differences according to ORV outcome"UK
negatively correlated ns positively correlated
age 13 8 4
IgA 0 24 0
seroconv 0 25 0 taxon Estimate Std.Error padj comparison
2 Escherichia/Shigella 0.045 0.013 1.727273e-03 age
3 Streptococcus -0.119 0.024 5.312500e-06 age
4 Staphylococcus -0.435 0.025 1.825000e-35 age
7 Lactobacillus -0.068 0.035 7.812500e-02 age
8 Collinsella -0.024 0.013 7.941176e-02 age
9 Haemophilus -0.226 0.023 1.125000e-16 age
10 Klebsiella -0.156 0.020 3.125000e-12 age
11 Enterococcus -0.116 0.024 1.194444e-05 age
14 Gemella -0.120 0.020 3.250000e-08 age
15 Enterobacter -0.050 0.017 7.142857e-03 age
16 Parabacteroides -0.051 0.016 2.500000e-03 age
17 Corynebacterium_1 -0.164 0.023 1.666667e-10 age
20 Granulicatella -0.063 0.015 1.225000e-04 age
22 Actinomyces -0.234 0.032 5.500000e-11 age
23 Eggerthella 0.146 0.018 1.916667e-12 age
24 Negativicoccus 0.058 0.021 1.016667e-02 age
25 Prevotella 0.256 0.078 2.500000e-03 ageSummary statistics
[1] "No significant differences according to ORV outcome"Dose 1 shedding
Number of infants/taxa included in longitudinal models:
- India (full), n infants: 305; n samples: 859; n taxa: 23
- India (exposed), n infants: 164; n samples: 459; n taxa: 24
- India (unexposed), n infants: 138; n samples: 391; n taxa: 22
- Malawi, n infants: 89; n samples: 189; n taxa: 43
- UK, n infants: 60; n samples: 171; n taxa: 21
India
ns
dose1 23Summary statistics
[1] "No significant differences according to ORV outcome"India (exposed)
ns
dose1 24Summary statistics
[1] "No significant differences according to ORV outcome"India (unexposed)
ns
dose1 22Summary statistics
[1] "No significant differences according to ORV outcome"Malawi
negatively correlated ns
dose1 1 41Summary statistics
taxon Estimate Std.Error padj comparison mean prev
28 Sutterella -1.418 0.369 0.00966 dose1 1.28 43.9Shedding after either dose
Number of infants/taxa included in longitudinal models:
- India (full), n infants: 304; n samples: 856; n taxa: 23
- India (exposed), n infants: 164; n samples: 459; n taxa: 24
- India (unexposed), n infants: 137; n samples: 388; n taxa: 22
- Malawi, n infants: 64; n samples: 135; n taxa: 42
- UK, n infants: 56; n samples: 160; n taxa: 22
India
negatively correlated ns
either 2 21Summary statistics
taxon Estimate Std.Error padj comparison mean prev
17 Corynebacterium_1 -0.342 0.110 0.02415 either 0.022 65.5
22 Dolosigranulum -1.069 0.339 0.02415 either 0.012 35.4India (exposed)
ns
either 24Summary statistics
[1] "No significant differences according to ORV outcome"India (unexposed)
negatively correlated ns
either 1 21Summary statistics
taxon Estimate Std.Error padj comparison mean prev
17 Corynebacterium_1 -0.769 0.246 0.0462 either 0.024 66.8Malawi
negatively correlated ns positively correlated
either 2 36 4Summary statistics
taxon Estimate Std.Error padj comparison mean prev
9 Haemophilus 1.430 0.461 0.084 either 0.404 40.0
10 Klebsiella 1.571 0.611 0.084 either 3.946 70.4
14 Gemella 0.919 0.351 0.084 either 0.029 64.4
26 Phascolarctobacterium 1.769 0.644 0.084 either 0.169 27.4
31 Holdemanella -1.701 0.569 0.084 either 0.172 28.1
36 Lawsonella -2.512 0.933 0.084 either 0.007 22.2.